ObjectiveTo investigate the mechanism of Biejiajian Wan in the intervention of primary liver cancer based on long non-coding RNA SNHG5 （lncRNA SNHG5）/micro RNA-26a-5p （miRNA-26a-5p）/glycogen synthase kinase-3β （GSK-3β） signal axis. MethodDouble luciferase reporting assay was used to verify the targeted interaction between lncRNA SNHG5 and miRNA-26a-5p， miRNA-26a-5p， and GSK-3β in HepG2 cells. Nude-mouse transplanted tumor model of human HepG2 were established and randomly divided into model group， Biejiajian Wan low-dose group （0.5 g·kg^-1）， medium-dose group （1.0 g·kg^-1）， and high-dose group （2.0 g·kg^-1）， and sorafenib group （100 mg·kg^-1）， with 10 mice in each group. The mice were given intragastric administration of normal saline or drug for 28 days， and the tumor volume was measured at different time. Hematoxylin-eosin （HE） staining was used to observe the histological changes of tumors. The nucleic acid levels of lncRNA SNHG5， miRNA-26a-5p， GSK-3β， and β-catenin mPNA in tumor tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of GSK-3β and β-catenin in tumor tissue were detected by western blot. ResultCompared with the SNHG5-WT （wild type） + miRNA NC （negative control） group， the relative luciferase activities of the SNHG5-WT + miRNA-26a-5p mimic group were decreased （P<0.05）. Compared with the GSK-3β-WT + miRNA NC group， the relative luciferase activity of the GSK-3β-WT + miRNA-26a-5p mimic group was decreased （P<0.05）. Compared with the model group， the tumor volume of Biejiajian Wan low-dose， medium-dose， and high-dose groups was significantly decreased （P<0.05， P<0.01）. Compared with the model group， the cells in the tumor tissue of nude mice in each dose group of Biejiajian Wan were sparsely arranged with necrocytosis， which showed concentration-dependent changes. Compared with the model group， the expression levels of lncRNA SNHG5， GSK-3β， and β-catenin were decreased （P<0.05， P<0.01）， while the expression of miRNA-26a-5p was increased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. Compared with the model group， the protein expression levels of GSK-3β and β-catenin were decreased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. ConclusionBiejiajian Wan may affect the necrosis of liver cancer cells through lncRNA SNHG5/miRNA-26a-5p/GSK-3β signal axis and thus play an anti-tumor role. This research will provide more theoretical basis for the clinical application of Biejiajian Wan.

OBJECTIVE To evaluate the comprehensive value of four first-line combination immunotherapy for unresectable hepatocellular carcinoma， and provide a reference for determining the optimal clinical treatment decision for unresectable hepatocellular carcinoma. METHODS R4.2 software was used for network meta-analysis to obtain the effect values of the efficacy and safety indicators of four combination therapies [atezolizumab combined with bevacizumab （AB）， sintilimab combined with bevacizumab biosimilars （SB）， camrelizumab combined with apatinib （CA）， durvalumab combined with tremelimumab （DT）]. Combined with the efficacy， safety and economic indicators， the categorical based evaluation technique （M-MACBETH） was used to establish the value tree. At the same time， the comprehensive value scores of four therapies were calculated， and sensitivity analysis was performed to evaluate the robustness. RESULTS In terms of prolonging median overall survival， the advantage order of the four therapies was ranked as SB， CA， AB and DT. In terms of extending median progression-free survival， the advantage order of the four therapies was CA， SB， AB and DT. In terms of safety， the order of advantages was DT， AB， SB and CA. In terms of economy， the order of advantages was CA， SB， AB and DT. The comprehensive scores of SB， CA， AB and DT were 67.11， 57.77， 52.53 and 42.59 points， respectively. The results of the sensitivity analysis showed that the ranking results of comprehensive value for four regimens were robust. CONCLUSIONS Among the four first-line immune combination therapies for unresectable hepatocellular carcinoma， SB is the optimal treatment regimen， followed by CA， AB and DT.

By organizing and studying on the original works of LI Wenrong， this paper aimed to explore his theories and methods for treating liver diseases. LI Wenrong believes that the liver is easily prone to physiological disturbances， difficult to pacify， and can be compared to a “chariot” that moves horizontally and vertically， acting as a “general” for both civil and military affairs. Pathologically， liver diseases tend to spread to other organs， resulting in ever-changing pathological changes， often affecting emotional health. In terms of therapeutic methods， LI Wenrong proposes ten methods including draining fire to calm the liver， nourishing water to moisten wood， clearing metal to calm the liver， calming gallbladder and harmonizing liver， subduing yang with shell-drug， treating liver diseases by supplementing spleen， soothing the liver with sweetness， astringing the liver with sourness， relieving the liver with spiciness， and draining the liver with excess-fire. These methods have great guidance and reference value for contemporary clinical practice in traditional Chinese medicine.

ObjectiveThis study aims to explore risk factors for the development of major adverse cardiovascular and cerebrovascular events （MACCEs） in middle-aged and elderly patients with type 2 diabetes mellitus complicated with stable angina pectoris （T2DM-SAP） based on real-world clinical data in traditional Chinese medicine （TCM）， so as to develop a COX proportional risk prediction model and visualize the predicted results using a nomogram. MethodBased on the clinical scientific research information sharing system， the medical records of 586 T2DM-SAP patients （45-94 years old） were collected from January 2012 to December 2019， including age， gender， course of disease， major medical history， laboratory examination， tongue image， pulse image， TCM syndrome， and major treatment drugs. MACCE outcome indicators of patients were obtained by telephone follow-up and re-hospitalization records. The data was divided into a training set and a validation set according to 7∶3. In the training set， COX univariate analysis was used to determine the risk factors for MACCE in T2DM-SAP patients， and then variables were screened by forward-backward stepwise regression method， so as to establish a MACCE risk prediction model and construct a nomogram. The predictive efficacy of the model was reflected by the C-index， receiver operating characteristic （ROC） curve， calibration map， and clinical decision curve. ResultThe history of cerebrovascular disease ［Hazard ratio （HR）=1.983， 95% confidence interval （CI，1.314-2.993）］， low-density lipoprotein （LDL-C/mmol·L^-1）≥4.1［HR=2.683， 95%CI（1.461-4.925）］， dull red tongue ［HR=1.955， 95%CI（1.273-3.002）］， dull purple tongue ［HR=4.214， 95%CI（2.017-8.803）］， white thick coating ［HR=3.030， 95%CI（1.634-9.293）］， thin and weak pulse ［HR=2.233， 95%CI（1.283-3.888）］， and syndrome of wind-phlegm blocking collaterals ［HR=2.007， 95%CI（1.179-3.418）］ were found to be risk factors in middle-aged and elderly T2DM-SAP patients. Insulin ［HR=0.604， 95%CI（0.399-0.914）］， glycosidase inhibitor ［HR=0.627， 95%CI（0.409-0.962）］， and TCM treatment ［HR=0.328， 95%CI（0.214-0.503）］ were protective factors in middle-aged and elderly T2DM-SAP patients. The prediction model was constructed based on the above risk factors. The C-index of the model was 0.818 （95% CI 0.777 -0.859） in the training set and 0.814 （95% CI 0.773-0.855） in the validation set， and the change of C-index over time was plotted. The AUC of patients for 5， 10， 15 years in the training set was 0.71， 0.67， and 0.61. The AUC of patients for 5， 10， and 15 years in the validation set was 0.60， 0.68， and 0.63， respectively. The calibration map and clinical decision curves of 5， 10， 15 years were drawn in the training set and the validation set， respectively. The model was well calibrated and clinically effective. ConclusionThe history of cerebrovascular disease， LDL， dull red tongue， dull purple tongue， white thick coating， thin and weak pulse， and syndrome of wind-phlegm blocking collaterals are risk factors for MACCE in middle-aged and elderly T2DM-SAP patients， and insulin， glycosidase inhibitors， TCM treatment are protective factors for MACCE in middle-aged and elderly T2DM-SAP patients. A clinical prediction model is established accordingly. This model has good discrimination， calibration degree， and clinical effectiveness and provides a scientific basis for the prevention and treatment of MACCE in middle-aged and elderly T2DM-SAP patients.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

The amount of data generated by the human experience in medical cases of classic formulas is large and the research value is high， but how to extract valuable information from these massive data is an important problem of researches on classical formulas. It is concluded that there are many problems in the current study of human experience in classical formulas， such as large amount of data， uneven quality， weak extrapolation and clinical application， which seriously affected the evidence strength of human experience in classical formulas and the contribution to experience accumulation and theoretical support. Therefore， from the structural perspective of the research questions， this paper proposed the research ideas of human experience in medical cases of classic formulas： firstly， according to the characteristics of traditional Chinese medicine （TCM） cases， based on the PICO model， which refers parti-cipants （P）， intervention （I）， comparisons （C）， and outcomes （O）， a TCM medical record evaluation tool in line with the evidence-based concept was constructed to evaluate the quality of medical cases； secondly， constructing a standardized database of human experience in classical formulas and using data mining algorithms to explore the deep relationship hidden in human experience； finally， the clinical value evaluation is carried out to verify the effectiveness of the diagnosis and treatment rules of classical formulas to achieve clinical transformation.

Objective The results of ASTRUM-007 reveal the clinical benefits of PD-L1-positive esophageal squamous cell carcinoma(ESCC)patients.This study aims to analyze the economics of first-line treatment of PD-L1-positive ESCC with brucella combined with chemotherapy from the perspective of China's health system.Methods A three-state partitioned survival model(PSM)including progression-free survival(PFS),disease progression(PD),and death(D)was established to evaluate the economy of serplulimab combined with chemotherapy,the first-line treatment for PD-L1 positive advanced ESCC,compared with the placebo combination chemotherapy.The cycle period was two weeks,the horizon of the simulation was a lifetime,and the annual discount rate was set to 5%.The main outcome parameters are total cost,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER).One-way sensitivity analysis(OWSA),probability sensitivity analysis(PSA),and scenario analysis were used to evaluate the impact of the change of important parameters in the model on ICER.Results The basic results showed that the incremental effect and incremental cost of the serplulimab combined with chemotherapy compared with the placebo combination chemotherapy were 1.281 QALYs and 266 573.26 yuan,respectively,and the ICER was 208 166.24 yuan/QALY.OWSA showed that the price of serplulimab was the most sensitive parameter to ICER;PSA showed that when the WTP threshold was three times China's per capita GDP in 2022,Serplulimab combined with chemotherapy was significantly more economical than the placebo combination chemotherapy;scenario analysis revealed that according to the ASTRUM-007 study in the Central Asian group and the charitable drug donation program of serplulimab:in patients with PD-L1 1≤CPS<10,ICER was 205 056.83 yuan/QALY;with 218 022.59/QALY in patients with PD-L1 CPS≥10,and the mean value of ICER was lower than three times of China's per capita GDP.The ICER of all patients was 59 046.65 yuan/QALY,with 68 294.42 yuan/QALY of patients with PD-L1 1≤CPS<10,44 744.02 yuan/QALY of patients with PD-L1 CPS≥10.The ICER value was lower than China's per capita GDP.Conclusion Serplulimab combined with chemotherapy is more economical than placebo combined with chemotherapy in the treatment of PD-L1-positive ESCC patients.

Objective To explore the classification and characteristics of common syndromes of primary liver cancer and provide reference for clinical treatment.Methods Collect the four diagnostic information of patients with primary liver cancer from two top three TCM hospitals in Henan Province,and build a database.Using Lantern 5.0 software,based on two-step hidden tree analysis,a hidden structure model was constructed,and common syndromes of primary liver cancer were extracted through comprehensive clustering.SPSS 23.0 software was used for factor analysis and systematic cluster analysis to infer the potential syndromes.Combined with the results of different methods and professional knowledge,the syndrome classification of primary liver cancer was determined.Results A total of 1353 patients with 105 symptoms of primary liver cancer were included.59 symptoms with an analysis frequency≥40 were included to construct a hidden structure model,24 hidden variables were obtained,and 5 common syndromes were obtained by comprehensive clustering,namely,qi deficiency syndrome,liver depression and qi stagnation syndrome,blood stasis syndrome,water dampness stagnation syndrome,liver and gallbladder damp heat syndrome.20 common factors were obtained by factor analysis for symptoms with frequency>3%,and 8 common syndromes were inferred by cluster analysis with common factors.7 common syndromes and characteristics were finally determined by combining different methods and expertise.Conclusion The common syndromes of primary liver cancer are qi deficiency syndrome,liver depression and qi stagnation syndrome,blood stasis syndrome,water dampness stagnation syndrome,yin deficiency syndrome,liver and gallbladder damp heat syndrome,spleen deficiency and dampness stagnation syndrome.The results objectively reflect the actual situation of patients with primary liver cancer,and can provide reference for the treatment of primary liver cancer based on syndrome differentiation.

OBJECTIVE To evaluate the cost-effectiveness of sintilimab combined with chemotherapy than single-use chemotherapy in the first-line treatment of advanced， recurrent or metastatic esophageal squamous cell carcinoma （ESCC） from the perspective of health system of our country， and provide reference for rational use of drug in clinic. METHODS Based on ORIENT-15 study data， TreeAge Pro 2011 software was used to establish a three-state Markov model of non-progressive survival （PFS）， disease progression and death for cost-utility analysis. The model period was 3 weeks， the research time limit was 10 years， and the discount rate was 5%. The main outputs of the model were total cost， quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER）. The 1-3 times of China’s GDP per capita in 2021 was taken as the threshold of willing- ness to pay （WTP）. The uncertainty of the parameters was analyzed by single factor sensitivity analysis and probability sensitivity analysis， and the cost-effectiveness of the two schemes was discussed under three situations： different discount rates， comparison with other similar treatment schemes and charitable drug donation schemes. RESULTS The results of basic analysis showed that compared with chemotherapy plan alone， the ICER of sintilimab combined with chemotherapy was 64 208.75 yuan/QALY， which was less than WTP threshold. The results of single factor sensitivity analysis show that PFS state utility value， cycle cost of sintilimab and discount rate had relatively great influence on the results. Probability sensitivity analysis showed that when WTP≥120 000 yuan， the economic probability of sintilimab combined with chemotherapy plan was 100%. The results of situational analysis showed that sintilimab combined chemotherapy was more cost- effective than single-use chemotherapy. CONCLUSIONS Sintilimab combined with chemotherapy is more cost-effective than single-use chemotherapy in the first-line treatment of advanced， recurrent or metastatic ESCC.

ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）. MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model. ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ²=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05. ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.